Monolithic biocompatible implantable laminated materials

ABSTRACT

Metal foils, wires, and seamless tubes with increased mechanical strength are provided. As opposed to wrought materials that are made of a single metal or alloy, these materials are made of two or more layers forming a laminate structure. Laminate structures are known to increase mechanical strength of sheet materials such as wood and paper products and are used in the area of thin films to increase film hardness, as well as toughness. Laminate metal foils have not been used or developed because the standard metal forming technologies, such as rolling and extrusion, for example, do not lend themselves to the production of laminate structures. Vacuum deposition technologies can be developed to yield laminate metal structures with improved mechanical properties. In addition, laminate structures can be designed to provide special qualities by including layers that have special properties such as superelasticity, shape memory, radio-opacity, corrosion resistance etc. Examples of articles which may be made by the inventive laminate structures include implantable medical devices that are fabricated from the laminated deposited films and which present a blood or body fluid and tissue contact surface that has controlled heterogeneities in material constitution. An endoluminal stent-graft and web-stent that is made of a laminated film material deposited and etched into regions of structural members and web regions subtending interstitial regions between the structural members. An endoluminal graft is also provided which is made of a biocompatible metal or metal-like material. The endoluminal stent-graft is characterized by having controlled heterogeneities in the stent material along the blood flow surface of the stent and the method of fabricating the stent using vacuum deposition methods.

CROSS-REFERENCE TO RELATED INVENTIONS

This application is a continuation of co-pending, commonly assignedapplication U.S. Ser. No. 15/432,546; which is a continuation of U.S.Ser. No. 11/047,024 filed Jan. 31, 2005, now U.S. Pat. No. 9,566,148;which is a continuation of U.S. patent application Ser. No. 09/853,985,filed May 11, 2001, now U.S. Pat. No. 6,849,085, issued Feb. 1, 2005;which claims priority from U.S. Provisional Patent Application Ser. No.60/203,835, filed May 12, 2000.

BACKGROUND OF THE INVENTION

The present invention pertains generally to implantable medical devicesand, more particularly, to implantable medical devices fabricated ofself-supporting laminated films fashioned into geometric configurationsadapted to specific medical uses. More particularly, the presentinvention relates to metal films, foils, wires and seamless tubes, withincreased mechanical properties, which are suitable for use infabricating implantable endoluminal grafts, stent-grafts andstent-graft-type devices. More specifically, the present inventioncomprises endoluminal grafts, stent-grafts and stent-graft-type devicesthat are fabricated entirely of self-supporting laminated films, foils,wires or seamless tubes made of biocompatible metals or of biocompatiblematerials which exhibit biological response and material characteristicssubstantially the same as biocompatible metals, such as for examplecomposite materials.

As opposed to wrought materials that are made of a single metal oralloy, these inventive materials are made of at least two layers formedupon one another into a self-supporting laminate structure. Laminatestructures are generally known to increase the mechanical strength ofsheet materials, such as wood or paper products. Laminates are used inthe field of thin film fabrication also to increase the mechanicalproperties of the thin film, specifically hardness and toughness.Laminate metal foils have not been used or developed because thestandard metal forming technologies, such as rolling and extrusion, forexample, do not readily lend themselves to producing laminatestructures. Vacuum deposition technologies can be developed to yieldlaminate metal structures with improved mechanical properties. Inaddition, laminate structures can be designed to provide specialqualities by including layers that have special properties such assuperelasticity, shape memory, radio-opacity, corrosion resistance etc.

Metal foils, wires and thin-walled seamless tubes are typically producedfrom ingots in a series of hot or cold forming steps that include somecombination of rolling, pulling, extrusion and other similar processes.Each of these processing steps is accompanied by auxiliary steps thatinclude cleaning the surfaces of the material of foreign materialresidues deposited on the material by the tooling and lubricants used inthe metal forming processes. Additionally, chemical interaction withtooling and lubricant materials and ambient gases also introducescontaminants. Some residue will still usually remain on the surface ofthe formed material, and there is a high probability that thesecontaminating residues become incorporated during subsequent processingsteps into the bulk of the wrought metal product. With decreasingmaterial product size, the significance of such contaminating impuritiesincreases. Specifically, a greater number of process steps, and,therefore, a greater probability for introducing contaminants, arerequired to produce smaller product sizes. Moreover, with decreasingproduct size, the relative size of non-metal or other foreign inclusionsbecomes larger. This effect is particularly important for materialthicknesses that are comparable to the grain or inclusion size. Forexample, austenitic stainless steels have typical grain sizes on theorder of magnitude of 10-100 micrometer. When a wire or foil with athickness in this range is produced, there is significant probabilitythat some grain boundaries or defects will extend across a large portionor even across the total thickness of the product. Such products willhave locally diminished mechanical and corrosion resistance properties.While corrosion resistance is remedied by surface treatments such aselectropolishing, the mechanical properties are more difficult tocontrol.

The mechanical properties of metals depend significantly on theirmicrostructure. The forming and shaping processes used to fabricatemetal foils, wires and thin-walled seamless tubes involves heavydeformation of a bulk material, which results in a heavily strained anddeformed grain structure. Even though annealing treatments may partiallyalleviate the grain deformation, it is typically impossible to revert towell-rounded grain structure and a large range of grain sizes is acommon result. The end result of conventional forming and shapingprocesses, coupled with annealing, typically results in non-uniformgrain structure and less favorable mechanical properties in smallersized wrought metal products. It is possible, therefore, to produce highquality homogeneous materials for special purposes, such asmicromechanical devices and medical devices, using vacuum depositiontechnologies.

In vacuum deposition technologies, materials are formed directly in thedesired geometry, e.g., planar, tubular, etc. The common principle ofthe vacuum deposition processes is to take a material in a minimallyprocessed form, such as pellets or thick foils (the source material) andatomize them. Atomization may be carried out using heat, as is the casein physical vapor deposition, or using the effect of collisionalprocesses, as in the case of sputter deposition, for example. In someforms of deposition, a process, such as laser ablation, which createsmicroparticles that typically consist of one or more atoms, may replaceatomization; the number of atoms per particle may be in the thousands ormore. The atoms or particles of the source material are then depositedon a substrate or mandrel to directly form the desired object. In otherdeposition methodologies, chemical reactions between ambient gasintroduced into the vacuum chamber, i.e., the gas source, and thedeposited atoms and/or particles are part of the deposition process. Thedeposited material includes compound species that are formed due to thereaction of the solid source and the gas source, such as in the case ofchemical vapor deposition. In most cases, the deposited material is theneither partially or completely removed from the substrate, to form thedesired product.

The rate of film growth is a significant parameter of vacuum depositionprocesses. In order to deposit materials that can be compared infunctionality with wrought metal products, deposition rates in excess of1 micrometers/hour are a must and indeed rates as high as 100micrometers per hour are desirable. These are high deposition rates andit is known that at such rates the deposits always have a columnarstructure. Depending on other deposition parameters, and mostimportantly on the substrate temperature, the columns may be amorphousor crystalline but at such high deposition rates microcrystallinestructure development can be expected at best. The difficulty is thatthe columns provide a mechanically weak structure in which crackpropagation can occur uninhibited across the whole thickness of thedeposit.

A special advantage of vacuum deposition technologies is that it ispossible to deposit layered materials and thus films possessingexceptional qualities may be produced (c.f., H. Holleck, V. Schier:“Multilayer PVD coatings for wear protection”, Surface and CoatingsTechnology, Vol. 76-77 (1995) pp. 328-336). Layered materials, such assuperstructures or multilayers, are commonly deposited to take advantageof some chemical, electronic, or optical property of the material as acoating; a common example is an antireflective coating on an opticallens.

It has not been recognized until relatively recently that multilayercoatings may have improved mechanical properties compared with similarcoatings made of a single layer. The improved mechanical properties maybe due to the ability of the interface between the layers to relievestress. This stress relief occurs if the interface provides a slideplane, is plastic, or may delaminate locally. This property ofmultilayer films has been recognized in regard with their hardness butthis recognition has not been translated to other mechanical propertiesthat are significant for metal products that may be used in applicationwhere they replace wrought metal parts.

A technological step that interrupts the film growth results indiscontinuous columns and prevents crack propagation across the entirefilm thickness. In this sense, it is not necessary that the structureconsist of a multiplicity of chemically distinct layers, as it is commonin the case of thin film technology where multilayers are used. Suchchemical differences may be useful and may contribute to improvedproperties of the materials.

In its simplest form, the inventive process consists of the steps ofproviding a substrate, depositing a first layer of material on thesubstrate, depositing a second layer of material on the first layer ofmaterial and optionally removing the layered material from thesubstrate. The last step is necessary in the case of making foils andseamless tubes but would be omitted in the case of making wires. In thislatter case, the substrate itself is a thin wire that becomes part ofthe final product. In more complex cases, the number of layers is morethan two. There is no limitation regarding the number of layers andregarding the thickness of each layer.

As used in this application a “layer” is intended to mean asubstantially uniform material limited by interfaces between it andadjacent other substantially homogeneous layers, substrate, orenvironment. The interface region between adjacent layers is aninhomogeneous region in which extensive thermodynamic parameters maychange. Different layers are not necessarily characterized by differentvalues of the extensive thermodynamic parameters but at the interface,there is a local change at least in some parameters. For example, theinterface between two steel layers that are identical in composition andmicrostructure may be characterized by a high local concentration ofgrain boundaries due to an interruption of the film growth process.Thus, the interface between layers is not necessarily different inchemical composition if it is different in structure.

It is necessary to provide for good adhesion between the layers and thisis usually achieved by providing for a relatively broad interface regionrather than for an abrupt interface. The width of the interface regionmay be defined as the range within which extensive thermodynamicparameters change. This range can depend on the interface areaconsidered and it may mean the extent of interface microroughness. Inother words, adhesion may be promoted by increased interfacemicroroughness between adjacent layers.

By providing for a layered structure, the inventive materials consist ofa controlled maximum size of grains and columns as extended defects inthe direction of the film growth (perpendicular to the layers). Thislimit of the grain or defect size results in materials that haveincreased mechanical strength and particularly increased toughnesscompared to their non-laminated counterparts, both deposited and wroughtmaterials. In addition, limiting the extent to which defects and grainboundaries reach across the laminate, corrosion resistance is alsoimproved.

Laminated materials will have additional advantages when chemicalcompositions of the layers are chosen to achieve special properties. Forexample, a radiopaque material such as Ta may form one layer of astructure while other layers are chosen to provide the material withnecessary mechanical and other properties.

Without limiting the scope of application of the present invention, thefollowing are specific examples of products or devices which may befabricated using the laminated film and process of the presentinvention: 1) an implantable graft fabricated of laminated films ofbiocompatible metals or biocompatible materials which exhibit in vivobiological and mechanical responses substantially the same asbiocompatible metals (hereinafter referred to as “metal-likematerials”); 2) an implantable stent-graft device in which a structuralcomponent, or stent, and a graft component are each fabricated oflaminated films of metal or metal-like materials; 3) an implantablestent-graft-type device in which a structural support, such as a stent,defines openings which are subtended by a web, with both the stent andthe web being formed as a single, integral, laminated film or tubularstructure and fabricated of metals or of metal-like materials, thisparticular embodiment is hereinafter referred to as a “web-stent;” and4) planar films, sheets or foils made of laminated biocompatible metalsor biocompatible materials, suitable for use as medical tissue patches,aerospace surfaces, such as leading edges of aircraft wings orhelicopter rotors, or as active surfaces on tail rudders or wing flapsof aircraft.

Graft Embodiment

As used herein the term “Graft” is intended to indicate any type oftubular member which exhibits integral columnar and circumferentialstrength and which has openings which pass through the thickness of thetubular member. In accordance with a preferred embodiment of theinvention, a graft member is formed as a discrete thin sheet or tube ofbiocompatible metals or metal-like material. A plurality of openings isprovided which pass transversely through the graft member. The pluralityof openings may be random or may be patterned. It is preferable that thesize of each of the plurality of openings be such as to permit cellularmigration through each opening, without permitting fluid flow therethrough. In this manner, blood cannot flow through the plurality ofopenings, but various cells or proteins may freely pass through theplurality of openings to promote graft healing in vivo. In accordancewith another aspect of the inventive graft embodiment, it iscontemplated that two graft members are employed, with an outer diameterof a first graft member being smaller than the inner diameter of asecond graft member, such that the first graft member is concentricallyengageable within a lumen of the second graft member. Both the first andsecond graft members have a pattern of a plurality of openings passingthere through. The first and second graft members are positionedconcentrically with respect to one another, with the plurality ofpatterned openings being positioned out of phase relative to one anothersuch as to create a tortuous cellular migration pathway through the wallof the concentrically engaged first and second graft members. In orderto facilitate cellular migration through and healing of the first andsecond graft members in vivo, it is preferable to provide additionalcellular migration pathways that communicate between the plurality ofopenings in the first and second graft members. These additionalcellular migration pathways may be imparted as 1) a plurality ofprojections formed on either the luminal surface of the second graft orthe abluminal surface of the first graft, or both, which serve asspacers and act to maintain an annular opening between the first andsecond graft members that permits cellular migration and cellularcommunication between the plurality of openings in the first and secondgraft members, or 2) a plurality of microgrooves, which may be random,radial, helical, or longitudinal relative to the longitudinal axis ofthe first and second graft members, the plurality of microgrooves beingof a sufficient size to permit cellular migration and propagation alongthe groove without permitting fluid flow there through, the microgroovesserve as cellular migration conduits between the plurality of openingsin the first and second graft members.

Stent-Graft Embodiment

In accordance with another preferred embodiment of the presentinvention, a graft member may be formed as either a thin sheet ofmaterial or as a tubular member, and mechanically joined to cover aplurality of structural support members. The graft member may be used tocover either a luminal or abluminal surface, or both, of an endoluminaldevice.

A stent-graft in accordance with the present invention may be formed byconjoining a discrete graft member with a plurality of structuralsupport members, such as a stent, by mechanically joining the graftmember to regions of the plurality of structural support members.Alternatively, a stent-graft may be formed by first forming, such as byvacuum deposition methods or by etching a pre-existing material blank, agraft member as a contiguous thin sheet or tube which projects outwardlyfrom at least one aspect of the plurality of structural members. Thethin sheet is then everted over the structural members and brought intoa position adjacent a terminal portion of the plurality of structuralmembers such that it covers one or both of the putative luminal orabluminal surfaces of the plurality of structural members. The graftmember is then mechanically joined at an opposing end, i.e., theputative proximal or the putative distal end of the plurality ofstructural members.

The stent-graft is formed entirely of a metal or metal-like material,which, as opposed to using conventional synthetic polymeric graftmaterials, the inventive graft material exhibits improved healingresponse.

Web-Stent Embodiment

In accordance with one of the embodiments of the present invention,there is provided a stent-graft-type device, termed a “web-stent” inwhich there is at least one of a plurality of structural members thatprovide a primary means of structural support for the webbed-stentdevice. The plurality of structural members may be arranged in anymanner as is known in the art of stent fabrication, e.g., single elementforming a circle or ellipse, a single or plural elements which form atubular diamond-like or undulating pattern, in which adjacent structuralmembers are spaced apart forming open regions or interstices betweenadjacent structural members. In the present invention, the intersticesor open regions between adjacent structural members are subtended by aweb of material that is the same material or a material exhibitingsimilar biological and mechanical response as the material that formsthe plurality of structural members. The web may be formed within all ora portion of the interstitial area or open regions between the pluralityof structural support members.

Method of Making Graft, Stent-Graft and Web-Stent

Finally, the present invention provides a method of fabricating thegraft, stent-graft and web-stent devices of the present invention. Theinventive method consists of forming the device by vacuum deposition ofa film, either as a planar sheet or as a tube, of a biocompatiblematerial, such as nickel-titanium alloys. The thickness of the depositedmaterial is determined by the particular embodiment being fabricated.After the deposited film is created, either additive or subtractivemethodologies are employed to define: the structural members, theinterstitial web regions, the graft regions and/or a plurality ofopenings through the deposited film. Alternatively, a pre-fabricatedstarting film of a biocompatible material, such as Nitinol, may beemployed, and the stent-pattern formed by vacuum deposition methods orby conventional metal forming techniques, or by removing regions of thepre-fabricated film to form the interstitial regions of the web-stentdevice.

Where a graft member is being fabricated, the thickness of the depositedor pre-fabricated starting film may be less than that where a web-stentis being formed, due to the absence of structural members in the graftmember. However, where a stent-graft or a web-stent is being fabricated,structural members may be formed by alternative methods. The structuralmembers may be formed by additive techniques by applying a pattern ofstructural members onto a film, such as by vacuum deposition techniquesor conventional metal forming techniques, such as laminating or casting.Second, subtractive or selective removal techniques may be employed toremove material from patterned regions on a film, such as by etching apattern of interstitial regions between adjacent structural membersuntil a thinner film is created which forms the web subtending theplurality of structural members. Where a pre-existing stent is employedas the structural members, obviously, the structural members do not needto be fabricated or formed.

In accordance with the best mode contemplated for the present invention,the graft, the plurality of structural members and the web arefabricated of the same or similar metals or metal-like materials. Inorder to improve healing response, it is preferable that the materialsemployed have substantially homogenous surface profiles at the blood ortissue contact surfaces thereof. A substantially homogeneous surfaceprofile is achieved by controlling heterogeneities along the blood ortissue-contacting surface of the material. The heterogeneities that arecontrolled in accordance with an embodiment of the present inventioninclude: grain size, grain phase, grain material composition,stent-material composition, and surface topography at the blood flowsurface of the stent. Additionally, the present invention providesmethods of making endoluminal devices having controlled heterogeneitiesin the device material along the blood flow or tissue-contacting surfaceof the device. Material heterogeneities are preferably controlled byusing conventional methods of vacuum deposition of materials onto asubstrate.

The surface of a solid, homogeneous material can be conceptualized ashaving unsaturated inter-atomic and intermolecular bonds forming areactive plane ready to interact with the environment. In practice, aperfectly clean surface is unattainable because of immediate adsorptionof airborne species, upon exposure to ambient air, of O, O₂, CO₂, SO₂,NO, hydrocarbons and other more complex reactive molecules. Reactionwith oxygen implies the formation of oxides on a metal surface, aself-limiting process, known as passivation. An oxidized surface is alsoreactive with air, by adsorbing simple, organic airborne compounds.Assuming the existence of bulk material of homogeneous subsurface andsurface composition, oxygen and hydrocarbons may adsorb homogeneously.Therefore, further exposure to another environment, such as the vascularcompartment, may be followed by a uniform biological response.

Current metallic vascular devices, such as stents, are made from bulkmetals made by conventional methods which employ many steps thatintroduce processing aides to the metals make stent precursors, such ashypotubes. For example, olefins trapped by cold drawing and transformedinto carbides or elemental carbon deposit by heat treatment, typicallyyield large carbon rich areas in 316L stainless steel tubingmanufactured by cold drawing process. The conventional stents havemarked surface and subsurface heterogeneity resulting from manufacturingprocesses (friction material transfer from tooling, inclusion oflubricants, chemical segregation from heat treatments). This results information of surface and subsurface inclusions with chemical compositionand, therefore, reactivity different from the bulk material. Oxidation,organic contamination, water and electrolytic interaction, proteinadsorption and cellular interaction may, therefore, be altered on thesurface of such inclusion spots. Unpredictable distributions ofinclusions such as those mentioned above provide unpredictable anduncontrolled heterogeneous surface available for interaction with plasmaproteins and cells. Specifically, these inclusions interrupt the regulardistribution pattern of surface free energy and electrostatic charges onthe metal surface that determine the nature and extent of plasma proteininteraction. Plasma proteins deposit nonspecifically on surfacesaccording to their relative affinity for polar or non-polar areas andtheir concentration in blood. A replacement process known as the Vromaneffect, Vroman L., The importance of surfaces in contact phasereactions, Seminars of Thrombosis and Hemostasis 1987; 13(1): 79-85,determines a time-dependent sequential replacement of predominantproteins at an artificial surface, starting with albumin, following withIgG, fibrinogen and ending with high molecular weight kininogen. Despitethis variability in surface adsorption specificity, some of the adsorbedproteins have receptors available for cell attachment and thereforeconstitute adhesive sites. Examples are: fibrinogen glycoproteinreceptor IIbIIIa for platelets and fibronectin RGD sequence for manyblood activated cells. Since the coverage of an artificial surface withendothelial cells is a favorable end-point in the healing process,favoring endothelialization in device design is desirable in implantablevascular device manufacturing.

Normally, endothelial cells (EC) migrate and proliferate to coverdenuded areas until confluence is achieved. Migration, quantitativelymore important than proliferation, proceeds under normal blood flowroughly at a rate of 25 μm/hr or 2.5 times the diameter of an EC, whichis nominally 10 μm. EC migrate by a rolling motion of the cell membrane,coordinated by a complex system of intracellular filaments attached toclusters of cell membrane integrin receptors, specifically focal contactpoints. The integrins within the focal contact sites are expressedaccording to complex signaling mechanisms and eventually couple tospecific amino acid sequences in substrate adhesion molecules (such asRGD, mentioned above). An EC has roughly 16-22% of its cell surfacerepresented by integrin clusters. Davies, P. F., Robotewskyi A., GriemM. L. Endothelial cell adhesion in real time. J. Clin. Invest. 1993;91:2640-2652, Davies, P. F., Robotewski, A., Griem, M. L., Qualitiativestudies of endothelial cell adhesion, J. Clin. Invest. 1994;93:2031-2038. This is a dynamic process, which implies more than 50%remodeling in 30 minutes. The focal adhesion contacts vary in size anddistribution, but 80% of them measure less than 6 μm², with the majorityof them being about 1 μm², and tend to elongate in the direction of flowand concentrate at leading edges of the cell. Although the process ofrecognition and signaling to determine specific attachment receptorresponse to attachment sites is incompletely understood, regularavailability of attachment sites, more likely than not, would favorablyinfluence attachment and migration. Irregular or unpredictabledistribution of attachment sites, that might occur as a result ofvarious inclusions, with spacing equal or smaller to one whole celllength, is likely to determine alternating hostile and favorableattachment conditions along the path of a migrating cell. Theseconditions may vary from optimal attachment force and migration speed toinsufficient holding strength to sustain attachment, resulting in cellslough under arterial flow conditions. Due to present manufacturingprocesses, current implantable vascular devices exhibit such variabilityin surface composition as determined by surface sensitive techniquessuch as atomic force microscopy, X-ray photoelectron spectroscopy andtime-of-flight secondary ion mass spectroscopy.

There have been numerous attempts to increase endothelialization ofimplanted stents, including covering the stent with a polymeric material(U.S. Pat. No. 5,897,911), imparting a diamond-like carbon coating ontothe stent (U.S. Pat. No. 5,725,573), covalently binding hydrophobicmoieties to a heparin molecule (U.S. Pat. No. 5,955,588), coating astent with a layer of blue to black zirconium oxide or zirconium nitride(U.S. Pat. No. 5,649,951), coating a stent with a layer of turbostraticcarbon (U.S. Pat. No. 5,387,247), coating the tissue-contacting surfaceof a stent with a thin layer of a Group VB metal (U.S. Pat. No.5,607,463), imparting a porous coating of titanium or of a titaniumalloy, such as Ti—Nb—Zr alloy, onto the surface of a stent (U.S. Pat.No. 5,690,670), coating the stent, under ultrasonic conditions, with asynthetic or biological, active or inactive agent, such as heparin,endothelium derived growth factor, vascular growth factors, silicone,polyurethane, or polytetrafluoroethylene, U.S. Pat. No. 5,891,507),coating a stent with a silane compound with vinyl functionality, thenforming a graft polymer by polymerization with the vinyl groups of thesilane compound (U.S. Pat. No. 5,782,908), grafting monomers, oligomersor polymers onto the surface of a stent using infrared radiation,microwave radiation or high voltage polymerization to impart theproperty of the monomer, oligomer or polymer to the stent (U.S. Pat. No.5,932,299).

Thus, the problems of thrombogenicity and re-endothelializationassociated with stents have been addressed by the art in various mannerswhich cover the stent with either a biologically active or an inactivecovering which is less thrombogenic than the stent material and/or whichhas an increased capacity for promoting re-endothelialization of thestent situs. These solutions, however, all require the use of existingstents as substrates for surface derivatization or modification, andeach of the solutions result in a biased or laminate structure builtupon the stent substrate. These prior art coated stents are susceptibleto delaminating and/or cracking of the coating when mechanical stressesof transluminal catheter delivery and/or radial expansion in vivo.Moreover, because these prior art stents employ coatings applied tostents fabricated in accordance with conventional stent formationtechniques, e.g., cold-forming metals, the underlying stent substrate ischaracterized by uncontrolled heterogeneities on the surface thereof.Thus, coatings merely are laid upon the heterogeneous stent surface, andinherently conform to the topographical heterogeneities in the stentsurface and mirror these heterogeneities at the blood contact surface ofthe resulting coating. This is conceptually similar to adding a coat offresh paint over an old coating of blistered paint; the fresh coatingwill conform to the blistering and eventually, blister and delaminatefrom the underlying substrate. Thus, topographical heterogeneities aretypically telegraphed through a surface coating. Chemicalheterogeneities, on the other hand, may not be telegraphed through asurface coating but may be exposed due to cracking or peeling of theadherent layer, depending upon the particular chemical heterogeneity.

The current invention entails creating materials specifically designedfor manufacture of grafts, stents, stent-grafts and other endoluminaldevices. According to a preferred embodiment of the invention, themanufacture of grafts, stents, stent-grafts and other endoluminaldevices is controlled to attain a regular, homogeneous atomic andmolecular pattern of distribution along their surface. This avoids themarked variations in surface composition, creating predictable oxidationand organic adsorption patterns and has predictable interactions withwater, electrolytes, proteins and cells. Particularly, EC migration issupported by a homogeneous distribution of binding domains that serve asnatural or implanted cell attachment sites, in order to promoteunimpeded migration and attachment. Based on observed EC attachmentmechanisms such binding domains should have a repeating pattern alongthe blood contact surface of no less than 1 μm radius and 2 μmborder-to-border spacing between binding domains. Ideally, theinter-binding domain spacing is less than the nominal diameter of anendothelial cell in order to ensure that at any given time, a portion ofan endothelial cell is in proximity to a binding domain.

SUMMARY OF THE INVENTION

In accordance with the present invention, there is provided a laminatedfilm structure and a method of making laminated film structurescomprised of at least two of a plurality of plied layers ofbiocompatible metals or biocompatible materials which exhibitsmechanical properties superior to those of a monolithic film structureof substantially equal thickness as the laminated film structure.

In accordance with the present invention, there is provided a web-stentdevice, fabricated of a laminated film, in which there is at least oneof a plurality of structural members that provides a primary means ofstructural support for the web-stent device. The plurality of structuralmembers is spaced apart to form open regions or interstices betweenadjacent structural members. In the present invention, a web ofmaterial, that is the same or similar to the material which forms theplurality of structural members, subtends the interstices or openregions between adjacent structural members. The web may be formedwithin all or a portion of the interstitial area or open regions betweenthe plurality of structural support members. Both the plurality ofinterconnected structural members and the web may be formed of initiallysubstantially planar materials or of initially substantially cylindricalmaterials.

In accordance with another preferred embodiment of the presentinvention, there is provided a stent-graft device in which a graftmember is formed as a laminated film of material and mechanically joinedto one or both of the proximal and distal ends of the plurality ofstructural support members, and covers that surface of the plurality ofstructural support members which is to form either the luminal orabluminal surface of the stent-graft device. The graft member may beformed either separately or as a contiguous thin-film projecting fromthe plurality of structural members. Where the graft member is formed asa contiguous thin-film projecting from the plurality of structuralmembers, the thin film is either abluminally everted or luminallyinverted and brought into a position adjacent to the plurality ofstructural members such that it covers either, or both, the luminal orabluminal surfaces or the plurality of structural members, then isattached at an opposing end, i.e., the putative proximal or the putativedistal end of the plurality of structural members.

In accordance with another embodiment of the invention, there isprovided a graft formed as a discrete laminated thin sheet or tube ofbiocompatible metal or metal-like materials. A plurality of openings isprovided which pass transversely through the graft member. The pluralityof openings may be random or may be patterned. It is preferable that thesize of each of the plurality of openings be such as to permit cellularmigration through each opening, without permitting fluid flow therethrough. In this manner, blood cannot flow through the plurality ofopenings, but various cells or proteins may freely pass through theplurality of openings to promote graft healing in vivo.

In accordance with another aspect of the inventive graft embodiment, itis contemplated that two graft members are employed, one or both of thegraft members being formed of laminated films. An outer diameter of afirst graft member is dimensioned smaller than an inner diameter of asecond graft member, such that the first graft member is concentricallyengageable within a lumen of the second graft member. Both the first andsecond graft members have a plurality of patterned openings passingthere through. The first and second graft members are positionedconcentrically with respect to one another, with the plurality ofpatterned openings being positioned out of phase relative to one anothersuch as to create a tortuous cellular migration pathway through the wallof the concentrically engaged first and second graft members. In orderto facilitate cellular migration and healing of the first and secondgraft members, it is preferable to provide additional cellular migrationpathways that communicate between the plurality of openings in the firstand second graft members. These additional cellular migration pathwaysmay be imparted as 1) a plurality of projections formed on either theluminal surface of the second graft or the abluminal surface of thefirst graft, or both, which serve as spacers and act to maintain anannular opening between the first and second graft members and permitcellular migration in order to communicate between the plurality ofopenings in the first and second graft members, or 2) a plurality ofmicrogrooves, which may be random, radial, helical, or longitudinalrelative to the longitudinal axis of the first and second graft members,the plurality of microgrooves being of a sufficient size to permitcellular migration and propagation along the groove without permittingfluid flow there through, the microgrooves serve as cellular migrationconduits between the plurality of openings in the first and second graftmembers.

The present invention also provides a method of fabricating theweb-stent device which entails providing a planar or tubular laminatedfilm of a biocompatible material, such as forming the film by vacuumdeposition, then removing interstitial regions until a thinner filmregion is created which forms a web subtending a plurality of structuralmembers. Alternatively, a pre-existing conventionally produced sheet ortube of a biocompatible material, such as Nitinol, may be etched until athinner film is created in the etched regions, thereby forming theinterstitial web areas of the web-stent device.

Finally, in accordance with the present invention, there is provided animplantable endoluminal device that is fabricated from laminated filmmaterials that present a blood or tissue contact surface that issubstantially homogeneous in material constitution. More particularly,the present invention provides an endoluminal graft, stent, stent-graftand web-stent that is made of a material having controlledheterogeneities along the blood flow or tissue-contacting surface of thestent.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A is a perspective, partial cross-sectional view of a laminatedfilm sheet structure in accordance with the present invention.

FIG. 1B is a perspective, partial cross-sectional view of a laminatedfilm tubular structure in accordance with the present invention.

FIG. 2 is a perspective view of a preferred embodiment of the web-stentof the present invention.

FIG. 3 is a perspective view of a stent-graft in accordance with thepresent invention.

FIG. 4 is a perspective view of an alternative embodiment of theinventive stent-graft.

FIG. 5 is a cross-sectional view taken along line 5-5 of FIG. 4.

FIG. 6 is a cross-sectional view illustrating a pair of support membersand a section of interstitial web between adjacent supporting members.

FIG. 7 is a cross-sectional view illustrating a pair of support membersand a section of interstitial web between adjacent supporting members inaccordance with an alternative embodiment of the present invention.

FIG. 8A is a top plan view of a graft or web region with a plurality ofopenings passing there through.

FIG. 8B is a top plan view of an alternative embodiment of a graft orweb region of the present invention with a plurality of openings passingthere through.

FIG. 8C is a top plan view of a third embodiment of a graft or webregion of the present invention with a plurality of openings passingthere through.

FIG. 9A is a transverse cross-sectional view of a first embodiment of agraft member in accordance with the present invention.

FIG. 9B is a transverse cross-sectional view of a second embodiment of agraft member in accordance with the present invention.

FIG. 10 is a flow chart diagrammatically illustrating the method offabricating the laminated film graft, stent-graft and/or web-stent ofthe present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

According to the present invention, stent, web-stent and stent-graftdevices are provided which preferably exhibit substantially homogenoussurface properties. The inventive graft, stent, stent-graft andweb-stent devices may be depositing at least two layers of abiocompatible material to form a plied film, either in a planar orcylindrical conformation, then either adding a pattern of supportmembers to the film or removing at least some regions of the plied filmto create thinner regions in the starting film and defining relativelythinner and thicker film regions, such as thinner web regions betweenadjacent structural members formed by thicker film regions and/orrelatively thinner graft regions. An additive methodology may includevacuum deposition or lamination of a pattern of support members upon theplanar or cylindrical film. A subtractive methodology includes etchingunwanted regions of material by masking regions to form the structuralmembers and expose unmasked regions to the etchant. Additionally, inorder to improve in vivo healing, it is advantageous to impart openingspassing through the web or the graft. The openings are preferablyproduced during the process of forming the web or the graft. Theopenings in the web or the graft may be formed by conventional methodssuch as photolithographic processes, by masking and etching techniques,by mechanical means, such as laser ablation, EDM, or micromachining,etc. Suitable deposition methodologies, as are known in themicroelectronic and vacuum coating fabrication arts and incorporatedherein by reference, are plasma deposition and physical vapor depositionwhich are utilized to impart a metal layer onto the stent pattern.

In accordance with an aspect of the present invention there is provideda vacuum deposited device that is fabricated of a material havingsubstantially homogeneous surface properties across the blood contactsurface of the device. Current manufacturing methods for fabricatingendoluminal stents fail to achieve the desired material properties ofthe present invention. As discussed above, stents are fabricated frombulk metals that are processed in a manner that incorporates processingaides to the base metal. Presently, stents are made from hypotubesformed from bulk metals, by machining a series of slots or patterns intothe hyptotube to accommodate radial expansion, or by weaving wires intoa mesh pattern.

The present invention consists of a stent made of a bulk material havingcontrolled heterogeneities on the luminal surface thereof.Heterogeneities are controlled by fabricating the bulk material of thestent to have defined grain sizes that yield areas or sites along thesurface of the stent having optimal protein binding capability. Thecharacteristically desirable properties of the inventive stent are: (a)optimum mechanical properties consistent with or exceeding regulatoryapproval criteria, (b) controlling discontinuities, such as cracking orpinholes, (c) a fatigue life of 400 MM cycles as measured by simulatedaccelerated testing, (d) corrosion resistance, (e) biocompatibilitywithout having biologically significant impurities in the material, (f)a substantially non-frictional abluminal surface to facilitateatraumatic vascular crossing and tracking and compatible withtranscatheter techniques for stent introduction, (g) radiopaque atselected sites and MM compatible, (h) have a luminal surface which isoptimized for surface energy and microtopography, (i) minimalmanufacturing and material cost consistent with achieving the desiredmaterial properties, and (j) high process yields.

Controlling the surface profile of an endoluminal device is significantbecause blood protein interactions with surfaces of endoluminal devicesappear to be the initial step in a chain of events leading to tissueincorporation of the endovascular device. The present invention isbased, in part, upon the relationship between surface energy of thematerial used to make the endoluminal device and protein adsorption atthe surface of the endoluminal device. The present inventors have foundthat a relationship exists between surface free energy and proteinadsorption on metals commonly used in fabrication of endoluminaldevices. In addition, specific electrostatic forces resident on thesurface of metal endoluminal stents have been found to influence bloodinteractions with the stent surface and the vascular wall.

In accordance with a preferred embodiment the present invention, theinventive grafts, stent-grafts and web-stents have surface profileswhich are achieved by fabricating the graft, stent-graft and web-stentby the same metal deposition methodologies as are used and standard inthe microelectronic and nano-fabrication vacuum coating arts, and whichare hereby incorporated by reference. In accordance with a preferredembodiment the present invention, the preferred deposition methodologiesinclude ion-beam assisted evaporative deposition and sputteringtechniques. In ion beam-assisted evaporative deposition it is preferableto employ dual and simultaneous thermal electron beam evaporation withsimultaneous ion bombardment of the material being deposited using aninert gas, such as argon, xenon, nitrogen or neon. Bombardment withinert gas ions during deposition serves to reduce void content byincreasing the atomic packing density in the deposited material. Thereduced void content in the deposited material allows the mechanicalproperties of that deposited material to be similar to the bulk materialproperties. Deposition rates up to 20 nm/sec are achievable using ionbeam-assisted evaporative deposition techniques.

When sputtering techniques are employed, a 200-micron thick stainlesssteel film may be deposited within about four hours of deposition time.With the sputtering technique, it is preferable to employ a cylindricalsputtering target, a single circumferential source that concentricallysurrounds the substrate that is held in a coaxial position within thesource.

Alternate deposition processes which may be employed to form the stentin accordance with the present invention are cathodic arc, laserablation, and direct ion beam deposition. As known in the metalfabrication arts, the crystalline structure of the deposited filmaffects the mechanical properties of the deposited film. Thesemechanical properties of the deposited film may be modified bypost-process treatment, such as by, for example, annealing.

Materials to make the inventive graft, stent-graft and web-stent arechosen for their biocompatibility, mechanical properties, i.e., tensilestrength, yield strength, and their ease of deposition include, withoutlimitation, the following: elemental titanium, vanadium, aluminum,nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium,niobium, scandium, platinum, cobalt, palladium, manganese, molybdenumand alloys thereof, such as zirconium-titanium-tantalum alloys, nitinol,and stainless steel.

During deposition, the chamber pressure, the deposition pressure and thepartial pressure of the process gases are controlled to optimizedeposition of the desired species onto the substrate. As is known in themicroelectronic fabrication, nano-fabrication and vacuum coating arts,both the reactive and non-reactive gases are controlled and the inert ornon-reactive gaseous species introduced into the deposition chamber aretypically argon and nitrogen. The substrate may be either stationary ormoveable; either rotated about its longitudinal axis, moved in an X-Yplane, planatarily or rotationally moved within the deposition chamberto facilitate deposition or patterning of the deposited material ontothe substrate. The deposited material may be deposited either as auniform solid film onto the substrate, or patterned by (a) impartingeither a positive or negative pattern onto the substrate, such as byetching or photolithography techniques applied to the substrate surfaceto create a positive or negative image of the desired pattern or (b)using a mask or set of masks which are either stationary or moveablerelative to the substrate to define the pattern applied to thesubstrate. Patterning may be employed to achieve complex finishedgeometries of the resultant structural supports, web-regions or graft,both in the context of spatial orientation of patterns of regions ofrelative thickness and thinness, such as by varying the thickness of thefilm over its length to impart different mechanical characteristicsunder different delivery, deployment or in vivo environmentalconditions.

The device may be removed from the substrate after device formation byany of a variety of methods. For example, the substrate may be removedby chemical means, such as etching or dissolution, by ablation, bymachining or by ultrasonic energy. Alternatively, a sacrificial layer ofa material, such as carbon, aluminum or organic based materials, such asphotoresists, may be deposited intermediate the substrate and the stentand the sacrificial layer removed by melting, chemical means, ablation,machining or other suitable means to free the stent from the substrate.

The resulting device may then be subjected to post-deposition processingto modify the crystalline structure, such as by annealing, or to modifythe surface topography, such as by etching to expose a heterogeneoussurface of the device.

The present invention, therefore, consists of both a material and aprocess of making the inventive material. The inventive material is onefor which mechanical strength and toughness is important, among othercharacteristics. In accordance with the best mode presently contemplatedfor the invention, the inventive material consists of several layers of316L stainless steel, each of about 10 micrometers thick with nochemical differences between them. The layers are defined by interfacesbetween them that have an interface microroughness in excess of 2 nmrms. The cumulative thickness of the stainless steel film formed fromthis material is about 100 micrometers.

The inventive material is preferably made by positioning a cylindricalcopper mandrel along the axis of a cylindrical DC magnetron sputteringdevice. After the routine preparatory steps of obtaining a vacuum,admitting Argon sputtering gas, and cleaning the surface of the 316Lstainless steel target, film deposition is carried out at a rate of 50micrometers per hour for 12 minutes to obtain the first 10 micrometerthick layer. During the deposition, a negative bias voltage of 120 V isapplied to the mandrel. The film grows and has a columnar structure inwhich columns reach though the whole thickness. After the first layer isdeposited, the deposition process is interrupted for a brief period oftime (˜1 min). This time is sufficient for the formation of anadsorptive layer on the freshly deposited film. When the deposition isresumed, this adsorptive layer gives rise to columnar growth that thatis different from the columnar growth of the previous layer only in thatthe columns are not continuous. The deposition process steps are thenrepeated until the desired cumulative material thickness is attained. Atthat point, the material, still on the mandrel, is removed from thevacuum deposition chamber and the copper mandrel is chemically removed.Additional post-deposition steps of surface finishing, cutting, etc. maybe employed.

Turning now to the Figures, there is illustrated alternative preferredembodiments of the present invention. In FIGS. 1A and 1B there isillustrated a multi-layered plied film in accordance with the presentinvention. The inventive film 10 consists of a plurality of individuallayers 11 laminated upon one another to form the film 10. The individuallayers may be made of the same biocompatible material, such as abiocompatible metal, or may be made of discrete biocompatible materials.

With reference to FIG. 2, there is illustrated a web-stent 20 inaccordance with the present invention. The web-stent 20 is formed of avacuum deposited laminated planar or cylindrical film 10. The web-stent20 is formed by masking regions of the material blank which are to forma plurality of structural members 22, and then etching the unmaskedregions which then form interstitial webs 24 which subtend interstitialregions between adjacent structural members 22. The interstitial webs 24are etched to a material thickness that is less than the thickness ofthe plurality of structural members 22. It is preferable to impart aplurality of openings in the interstitial webs 24 in order to permitendothelialization of the luminal surface 26 of the interstitial webs24. The openings may be imparted as a random pattern or as a regularpattern in the interstitial web 24, as will be discussed hereinafter.

With reference to FIG. 3 there is depicted a stent-graft 30 inaccordance with the present invention. Stent-graft 30 is formed eitherfrom a tubular or planar laminated film 10, which is etched to form theplurality of structural members 32 and interstitial regions 34 betweenthe structural members 32. In addition, either or both a proximal 36 ora distal 38 graft region of the stent are provided and project outwardlyfrom terminal structural members 32. The proximal graft region 36 andthe distal graft region 38 are preferably etched to a reduced thicknessof less than the thickness of the structural members, and are made withopenings passing there through which promote cellular migration, as willbe discussed hereinafter.

Under certain applications it may be useful to employ the stent-graft 30with either or both of the proximal 36 or distal 38 graft regionsprojecting outwardly from the structural supports 32. Additionally, oneor more of the plied individual layers 11 that comprise the laminatefilm 10 may project outwardly from the structural supports 32. Analternative embodiment of the invention is illustrated in FIGS. 4 and 5.The alternative embodiment of the stent-graft 30 involves covering theluminal and abluminal surfaces of a plurality of structural supports 32with a luminal graft 36 and an abluminal graft 38. The luminal graft 36may initially be formed as the proximal graft region 36 in FIG. 3 and beluminally inverted 39 and passed into the lumen defined by thestructural members 32. The abluminal graft 38 may initially be formed asthe distal graft region 38 in FIG. 3 and be abluminally everted 37 overthe structural members 32. Alternatively, the luminal graft 36 and theabluminal graft 38 may be formed as either pre-fabricated discrete graftmembers made of biocompatible metal or metal-like materials that areeither tubular or planar then formed into a tube and concentricallyengaged about the plurality of structural members 32. Portions of eachof the abluminal graft 38 and the luminal graft 36 are mechanicallyjoined to the plurality of structural members 32 or to one and other,thereby effectively encapsulating the plurality of structural members 32between the luminal graft 36 and the abluminal graft 38. It ispreferable that opposing free ends of each of the abluminal graft 38 andluminal graft 36 are mechanically joined to and co-terminus with aterminal portion of the plurality of structural members 32. Mechanicaljoining may be accomplished by methods such as welding, suturing,adhesive bonding, soldering, thermobonding, riveting, crimping, ordovetailing. In accordance with an alternate embodiment of theinvention, the interstitial regions 34 may be subtended by a web 34, asdiscussed hereinabove, with reference to FIGS. 1 and 2.

Those of ordinary skill in the art, will understand and appreciate thatalternative methods of removing material from areas that form relativelythinner regions of the stent, web-stent or stent-graft may be employed.For example, in addition to chemical etching, relatively thinner regionsmay be formed by removing bulk material by ion milling, laser ablation,EDM, laser machine, electron beam lithography, reactive ion etching,sputtering or equivalent methods which are capable of reducing thethickness of the material in either the graft region or the interstitialweb region between the structural members. Alternatively, the structuralmembers may be added to the defined interstitial web or graft regions toform the device, or the interstitial web or graft regions may be addedto pre-existing structural members. Additive methods that may beemployed include conventional metal forming techniques, includinglaminating, plating, or casting.

Similarly, a wide variety of initial bulk material configurations may beemployed, including a substantially planar sheet substrate, an arcuatesubstrate or a tubular substrate, which is then processed by eithersubtractive or additive techniques discussed above.

By forming the structural members, the interstitial web and/or the graftof an integral, monolithic material, both the circumferential or hoopstrength of the resultant device, as well as the longitudinal orcolumnar strength of the device are enhanced over conventionalstent-graft devices. Additional advantages of the present invention,depending upon fabrication methods, may include: controlled homogeneityand/or heterogeneity of the material used to form the device bydeposition methodologies, enhanced ability to control dimensional andmechanical characteristics of the device, the ability to fabricatecomplex device conformations, ability to pattern and control theporosity of the web and/or graft regions, and a monolithic one-piececonstruction of a device which yields a minimized device profile andcross-sectional area. The devices of the present invention haverelatively thicker and thinner regions, in which the thinner regionspermit radial collapse of the device for endoluminal delivery. Theinventive device exhibits superior column strength that permits smallerintroducer size and more readily facilitates deployment of the device.

As illustrated in FIGS. 6 and 7, the web and/or graft regions, 44, 54between adjacent structural members 42, 52 may be co-planar with eitherthe luminal or abluminal surface of the structural members 42, or may bepositioned intermediate the luminal 51 and abluminal 56 surfaces of thestructural members 52.

In accordance with a preferred embodiment of the present invention, theweb regions of the inventive web-stent, the graft regions of theinventive stent-graft and the inventive graft have a plurality ofopenings which pass through the thickness of the material used tofabricate the inventive devices. Each of the plurality of openings isdimensioned to permit cellular migration through the opening withoutpermitting blood leakage or seepage through the plurality of openings.The plurality of openings may be random or may be patterned. However, inorder to control the effective porosity of the device, it is desirableto impart a pattern of openings in the material used to fabricate theinventive device.

FIGS. 8A-8C depict several examples of patterned openings in a sectionof material used to make the inventive web-stent, graft regions of thestent-graft, and the inventive graft. FIG. 8A depicts a material 60 witha plurality of circular openings 64 passing through the materialsubstrate 62. The plurality of circular openings is patterned in aregular array of rows and columns with regular inter-opening spacing 65between adjacent openings. In the particular embodiment illustrated thediameter of each of the plurality of openings is about 19 μm, with aninter-opening spacing in each row and column of about 34 μm on center.The thickness of the material 62 is approximately 10 μm. FIG. 8Billustrates another example of a pattern of a plurality of openingsuseful in the present invention. The material 62, which again isapproximately 10 μm in thickness, has a plurality of openings 66 and 67passing there through. The pattern of the plurality of openings 66 and67 is an alternating slot pattern in which the plurality of openings 66are arrayed adjacent one and other forming a y-axis oriented array 68relative to the material 62, while a plurality of openings 67 arearrayed adjacent one and other forming an x-axis oriented array 69relative to the material 62. The y-axis-oriented array 68 and thex-axis-oriented array 69 are then positioned adjacent one and other inthe material 62. In this particular example, the inter-array spacingbetween the y-axis-oriented array 68 and the x-axis-oriented array 69 isabout 17 μm, while each of the plurality of openings has a length ofabout 153 μm and a width of about 17 μm. Finally, FIG. 8C illustrates amaterial 60 in which the material substrate 62 has a regular array of aplurality of diamond-shaped openings 63 passing through the materialsubstrate 62. As with the alternative embodiments exemplified in FIGS.8A and 8B, the dimension of the plurality of diamond-shaped openings 63is of sufficient size to permit cellular migration through the openings63, while preventing blood flow or seepage through the plurality ofopenings 63.

FIGS. 9A and 9B illustrate alternate preferred embodiments of the graft70 and graft 80 in accordance with the present invention. Graft 70consists generally of concentrically positioned luminal graft member 74and abluminal graft member 72 and an interfacial region 74 where theluminal surface of the abluminal graft member 72 and the abluminalsurface of the luminal graft member 74 are in immediate juxtapositionwith one and other. Both the luminal 74 and the abluminal 72 graftmembers are fabricated in accordance with the methodologies describedabove, and are provided with a plurality of patterned openings 73 in theabluminal graft member 72 and a plurality of patterned openings 75 inthe luminal graft member 74. The plurality of patterned openings 74 and75 are positioned out of phase relative to one another. By positioningthe plurality of patterned openings 74 and 75 in an out-of-phaserelationship, there is no continuous opening that passes through theinterfacial region 76 which would permit blood flow or seepage from thelumen of the graft. However, in order to permit cellular migration fromthe abluminal surface of the graft to the lumen of the graft, theinterfacial region 76 should have microroughness [not shown] which isoriented either randomly or selectively, such as helically orcircumferential, about the interfacial region 76. The microroughnesspreferably has a peak-to-valley depth of between about 5μ to about 65μ,most preferably between about 10μ to 15μ, may be either on the luminalsurface of the abluminal graft 72 or on the abluminal surface of theluminal graft 74, or both. The microroughness spans the surface arearegion between adjacent pairs of openings 74, 75, and the microroughnessdepth permits cellular migration across the surfaces between adjacentopenings 74 and 75. The microroughness is not large enough to permitfluid passage through the inter-opening regions at the interface betweenthe luminal graft 74 and the abluminal graft 72. This property ofpermitting cellular growth is similar to the difference between theporosity of expanded polytetrafluoroethylene grafts which do not requirepre-clotting, and the much larger porosity of polyester or DACRON graftswhich require pre-clotting to prevent fluid seepage there from.

FIG. 9B illustrates an alternative embodiment of the inventive graft 80in which an abluminal graft member 82 is concentrically positioned abouta luminal graft member 84. Each of the abluminal graft member 82 and theluminal graft member 84 having a plurality of patterned openings 83, 85,respectively, passing there through. As with the embodiment depicted inFIG. 9A, the plurality of patterned openings 83 and 85 are positioned inan out-of-phase relationship to one and other in order to preventforming a continuous opening between the luminal and abluminal surfacesof the graft 80. However, unlike the embodiment in FIG. 9A, there is nocorresponding interfacial region 74. Rather, an annular open region 87is positioned intermediate the luminal graft member 84 and the abluminalgraft member 82. The annular open region 87 is created by providing aplurality of microprojections 86 that project either radially inwardfrom the luminal surface of the abluminal graft member 82 or radiallyoutward from the abluminal surface of the luminal graft member 84. Theplurality of microprojections 86 act as spacers which abut the opposingsurface of either the luminal graft member 84 or the abluminal graftmember 82 which bound the annular open region 87. The height of themicroprojections 86 and, therefore, the size of the annular open region87, are dimensioned such that cells may migrate through the annular openregion 87, while blood flow or seepage will not occur between the lumenand the abluminal surface of the graft 80.

According to a specific aspect of the graft embodiment of the presentinvention, the size of the plurality of openings in the luminal graftmember 74, 84 may be different than the size of the plurality ofopenings in the abluminal graft member 72, 82. For example, theplurality of openings in the abluminal graft member 74, 84 preferablyhave a larger size than the plurality of openings in the luminal graftmember 72, 84, while still retaining the out-of-phase relationshipbetween the plurality of openings in the luminal 72, 82 and theabluminal 74, 84 graft members. Where circular openings are provided, itis preferable that the luminal 72, 82 and the abluminal 74, 84 graftmembers have openings having diameters of between about 5 μm and 100 μm.

Additionally, a third member may be interposed between the luminal 72,82 and the abluminal 82, 84 graft members. The third member willpreferably have a very fine plurality of openings, such as on the orderof between 2-10μ, and permits use of a higher porosity in the luminaland abluminal grafts, without the need to maintain an out-of-phaserelationship between the openings in the luminal 72, 82 and theabluminal 74, 84 graft members.

Finally, the method 90 for fabricating the inventive grafts,stent-grafts and web-stents of the invention is illustrated in theprocess flow diagram in FIG. 10. As previously discussed above, astarting blank of material by vacuum depositing a starting blank of abiocompatible metal or metal-like laminated film 94. Then adetermination is made whether to employ an additive or a subtractivemethod 96 for forming the graft, stent-graft or web-stent. If anadditive method is selected 97, the structural supports are built uponthe starting blank 100, either by vacuum deposition techniques or byconventional metal forming techniques. If a subtractive method isselected 95, the regions to remain are masked 98, then the unmaskedregions are removed, such as by chemical etching or sputtering, to formthe interstitial web regions, graft regions and/or openings in eitherthe interstitial web regions and/or graft regions 99.

The following examples are provided in order to illustrate thealternative embodiments of the invention, and are not intended to limitthe scope of the invention.

Example 1: Stent Formation by Sputtering

A ceramic cylindrical substrate is introduced into a deposition chamberwith capabilities of glow discharge substrate cleaning and sputterdeposition of carbon and stainless steel. The deposition chamber isevacuated to a pressure less than or equal to 2×10⁻⁷ Torr. Pre-cleaningof the substrate is conducted under vacuum by glow discharge. Thesubstrate temperature is controlled to achieve a temperature betweenabout 300 and 1100 degrees Centigrade. A bias voltage between −1000 and+1000 volts is applied to the substrate sufficient to cause energeticspecies arriving at the surface of the substrate to have hyperthermalenergy between 0.1 eV and about 700 eV, preferably between 5-50 eV. Thedeposition sources are circumferential and are oriented to deposit fromthe target circumferentially about the substrate.

During deposition, the deposition pressure is maintained between 0.1 and10 mTorr. A sacrificial carbon layer of substantially uniform thickness(∀5%) between 10 and 500 Angstroms is deposited circumferentially on thesubstrate. After depositing the carbon layer, a cylindrical film ofstainless steel is deposited onto the sacrificial carbon layer on thecylindrical substrate at a deposition rate between about 10 to 100microns/hour. After formation of the stainless steel film, the substrateis removed from the deposition chamber and heated to volatilize theintermediate sacrificial carbon layer between the substrate and thefilm. After removing the carbon intermediate layer, the stainless steelfilm is removed from the substrate and exhibits material propertiessimilar to the bulk stainless steel target and surface propertiescharacterized by controlled heterogeneities in grain size, materialcomposition and surface topography. A series of patterns are thenmachined into the resultant stainless steel film to form a stent byelectrical discharge machining (EDM) or laser cutting the film.

Example 2: Stent Formation by Sputtering

The same operating conditions are followed as in Example 1, except thatthe substrate is tubular and selected to have a coefficient of thermalexpansion different than that of the resultant stent. No intermediatelayer of sacrificial carbon is deposited onto the substrate, and theouter surface of the substrate is etched with a pattern of recessesdefining a desired stent pattern. The substrate is mounted onto arotational jig within the deposition chamber and rotated at a uniformrate during deposition. Tantalum is used as the target material anddeposited into the recesses of the substrate from a single stationarysource. After deposition, the temperature of the substrate and thedeposited stent are controlled to impart diametric differential in thesubstrate and stent and permit removal of the stent from the substrate.

Example 3: Stent Formation by Ion Beam-Assisted Evaporative Deposition

A cylindrical substrate is introduced into a deposition chamber that hascapabilities of: substrate rotation and precise positioning, glowdischarge substrate cleaning, ion beam-assisted evaporative deposition,and cylindrical magnetron sputtering. The deposition sources are (a)dual electron beam evaporative sources placed adjacent to one another atthe base of the deposition chamber at a fixed distance from thesubstrate, these are used with simultaneous argon ion impingement ontothe substrate from a controlled ion beam source, and (b) a cylindricalmagnetron sputtering source with a carbon target capable ofcircumferentially coating a carbon sacrificial layer of substantiallyuniform thickness of between 10 and 200 Angstroms onto the substrate.

The substrate temperature is controlled to achieve a substratetemperature between about 300 and 1100 degrees Centigrade. Thedeposition chamber is evacuated to a pressure less than or equal to2×10⁻⁷ Torr. A pre-cleaning of the substrate is conducted under vacuumby glow discharge. The substrate is rotated to ensure uniform cleaningand subsequent uniform deposition thickness. After cleaning thesubstrate is moved into the magnetron and coated with the carbon layer.The substrate is then moved into position to receive the stent-formingmetal coating with simultaneous ion bombardment. One electron beamevaporation source contains titanium while the other source containsnickel. The evaporation rates of each of the titanium and nickelevaporation sources are separately controlled to form a nitinol alloy onthe substrate as the stent-forming metal.

Example 4: Planar Deposition of Stent

The same operating conditions of Example 3 are followed, except that aplanar substrate is used. The deposition source is a single electronbeam evaporation source containing platinum and is used withsimultaneous argon ion impingement onto the substrate from a controlledion beam source.

The substrate temperature is controlled to achieve a substratetemperature between about 300 and 1100 degrees Centigrade. Thedeposition chamber is evacuated to a pressure less than or equal to2×10⁻⁷ Torr. A pre-cleaning of the substrate is conducted under vacuumby glow discharge. After cleaning the substrate is moved into positionwithin the deposition chamber and coated with platinum from the electronbeam evaporation source with simultaneous argon ion bombardment, withthe electron beam evaporation source passing platinum through a patternmask corresponding to a stent pattern which is interposed between thesource and the substrate to pass a pattern of platinum onto thesubstrate.

After deposition, the patterned stent is removed from the substrate androlled about a forming substrate to a cylindrical shape and opposingends of the planar stent material are brought into juxtaposition withone another and may be attached by laser welding or left uncoupled.

Example 5: Thin-Film Deposition with Stent-Graft Etch

The same conditions are employed as in Example 4, except that a uniformlayer of stent-forming material is deposited having a thickness of 150microns without patterning of the stent onto the deposited layer.Rather, a negative mask is applied to the deposited stent-formingmaterial, and a chemical etchant is introduced to etch a pattern ofstructural elements into the stent-forming metal. The etchant ispermitted to react with the metal until a thinner film web having athickness of between 2-75 microns, is present between adjacentstructural elements. After the thinner film web is formed, the etchingis stopped, and the resultant stent-graft is removed and formed into atubular shape.

Example 6: Dry Etching Method

The same conditions as in Example 5 are followed, except that reactiveion etching is employed to form the thinner film web.

Example 7: Stent-Graft Formation

The same conditions are followed as in Example 5, except that thestructural elements are defined in an intermediate region of a tubularsubstrate, and interstitial regions between adjacent structural elementsare etched by chemical etching until interstitial openings are formedbetween adjacent structural elements while masking the structuralelements and proximal and distal regions of the tubular substrate.Proximal and distal graft regions are formed adjacent the intermediateregion of the tubular substrate and contiguous with the plurality ofstructural elements, by masking the structural elements and interstitialopenings and chemical etching the proximal and distal regions of thetubular substrate to yield a thinner film of material in the proximaland distal regions of the tubular substrate. The proximal and distalgraft regions are then everted, with the proximal graft region beinginverted luminally through the lumen of the structural members and thedistal graft region being everted abluminally over the structuralmembers. The proximal graft region is mechanically joined to the distalterminal end of the plurality of structural members, while the distalgraft region is mechanically joined to the proximal terminal end of theplurality of structural members, thereby encapsulating the plurality ofstructural members between the everted proximal and distal graftregions.

Example 8: Stent-Graft Formation—Discrete Graft and Discrete Stent

A pre-fabricated self-expanding superelastic shape memory alloy stent isprovided. Two cylindrical hypotubes of a superelastic shape memorymaterial similar to that of the stent are chemically etched to asubstantially uniform thickness of 10 μm, with a first hypotube havingan inner diameter which is of sufficient size to accommodate the outerdiameter of the stent, and a second hypotube having an outer diameterdimensioned to accommodate the inner diameter of the stent. The etchedhypotubes are then placed into a vacuum chamber and a cylindricalpattern mask having a regular array of circular openings, each circularopening having a diameter of about 25 μm, is positioned concentricallyabout each of the cylindrical hypotubes. The etched hypotubes arereactive ion etched to transfer the masked pattern to the etchedhypotube and impart a pattern of circular openings that pass through thewall thickness of the etched hypotubes corresponding to the maskpattern. The stent, and first and second etched and reactive ion etchedhypotubes are concentrically engaged upon one and other, with the secondhypotube being concentrically positioned within the lumen of the stentand the first hypotube being concentrically positioned about theabluminal surface of the stent. Proximal and distal ends of the stent,the first hypotube and the second hypotube are mechanically joined bywelding and then trimmed by laser cutting to ensure that the proximaland distal ends are co-terminus.

Example 9: Graft Formation

A cylindrical mandrel is provided which is coated with a sacrificiallayer. A plurality of patterned recesses is defined in the sacrificiallayer. The mandrel is introduced into a deposition chamber and anickel-titanium alloy is vacuum deposited onto the mandrel, whilerotating the mandrel, until a uniform adherent layer of the depositednickel-titanium alloy covers the cylindrical mandrel. After deposition,the sacrificial layer is removed, and the uniform adherent layerdisengaged from the cylindrical mandrel, yielding the inventive graft,with openings corresponding to the plurality of patterned recesses inthe graft material.

Example 10: Planar Laminated Film

A vacuum chamber capable of being pumped to 5×10⁻⁷ Torr is provided withand installed within industry standard thin-film deposition equipmentdescribed as follows. An electron beam gun capable of evaporating metalsis placed at the base of the chamber. The gun crucible is filled with acharge of high purity aluminum. A film thickness and deposition ratecontrol and monitoring device is installed above and to the side of thegun, capable of monitoring and controlling incident power to the guncrucible in order to control deposition rate. A fixture to hold a planarsubstrate is installed fifty cm above and centered over the gun. Amoveable shutter is placed between the gun and the substrate fixture,such that at a given and appropriate time the shutter can be removedfrom the deposition path to allow deposition onto a substrate. Infraredheaters are installed in the chamber in a position that allowscontrolled heating of the substrate to 200 degrees C. An ion beam gun isinstalled in the chamber in such a position that a formed and controlledAr ion beam can be directed onto a substrate held in the substratefixture.

The following steps are taken to form a laminate/multilayer film on asubstrate. A section of 316L stainless steel sheet metal, 36″ square and0.016″ thick is attached to the substrate holding fixture to serve asthe deposition substrate. The chamber is pumped to a base pressure of5×10⁻⁷ Torr. The infrared heaters are engaged to heat and maintain thesubstrate at 200 degrees C. With the shutter in the deposition path, theelectron beam gun power is ramped up which heats and outgases thealuminum charge. The aluminum charge is heated to obtain a vaporpressure compatible with a deposition rate equivalent to 75 angstromsper second. Simultaneous with this, the ion beam gun is started and astable 200 volt Ar ion beam with the current density of 0.5 mA/cm² isformed, at a chamber pressure of 3×10⁻⁵ Torr.

When these conditions are reached and stabilized, the shutter is opened.An aluminum film of 5000 angstroms thickness is deposited onto thesubstrate. At this point the shutter is closed and the electron beam gunpower is reduced to zero. The ion beam gun remains running. The chamberis backfilled with oxygen to a pressure of 8×10−4 Torr. The shutterreopens allowing Ar ion impingement of the substrate in the oxygenenvironment for three minutes. At this point the shutter is closed andthe oxygen flow is ceased. The chamber is allowed to pump back down to3×10−5 Torr. The electron beam gun is restarted, which again outgasesthe aluminum charge and brings it to the appropriate deposition vaporpressure. The shutter reopens and a second aluminum layer of 5000angstrom thickness is deposited onto the substrate. Again the shutter isclosed and the electron beam gun power reduced to zero. This layer isthen Ar ion impinged in an oxygen backfilled environment as before. Thiscycle is repeated to form multiple successive layers as are required forform a multilayer film of 50 micron total thickness.

While the invention has been described with reference to its preferredembodiments, those of ordinary skill in the relevant arts willunderstand and appreciate that the present invention is not limited tothe recited preferred embodiments, but that various modifications inmaterial selection, deposition methodology, manner of controlling thematerial heterogeneities of the deposited stent material, and depositionprocess parameters may be employed without departing from the invention,which is to be limited only by the claims appended hereto.

What is claimed is:
 1. A medical device material comprising asubstantially monolithic structural member having plural layers selectedfrom the group of metal and metal-like materials and at least one of theplural layers being a radiopaque material, each of the plural layershaving a columnar grain structure, wherein adjacent layers of the plurallayers have a discontinuous columnar grain structure relative to eachother.
 2. The medical device material of claim 1, wherein the monolithicstructural member further comprises a shape memory or superelasticmaterial.
 3. The biocompatible implantable material according to claim2, wherein at least one of the plural layers further comprises amonolithic bulk material.
 4. The biocompatible implantable materialaccording to claim 1, wherein the structural member has at least onsurface thereof having controlled heterogeneities thereupon.
 5. Thebiocompatible implantable material according to claim 2, wherein atleast one of the plural layers is selected from the group consisting oftitanium, aluminum, nickel, tantalum, zirconium, chromium, platinum,cobalt, palladium, molybdenum and alloys thereof,zirconium-titanium-tantalum alloys, nitinol, and stainless steel.
 6. Thebiocompatible implantable material according to claim 1, furthercomprising an adsorptive layer between adjacent layers of the plurallayers.
 7. A biocompatible implantable material, comprising asubstantially monolithic structural member comprising an implantablemedical device, the substantially monolithic structural member havingplural layers selected from the group of metal and metal-like materials,at least one of the plurality of layers comprising a radiopaquematerial, each of the plural layers having a columnar grain structure,wherein adjacent layers of the plural layers have a discontinuouscolumnar grain structure relative to each other.
 8. The biocompatibleimplantable material according to claim 7, wherein at least one of theplural layers further comprises a monolithic bulk material.
 9. Thebiocompatible implantable material according to claim 7, wherein theimplantable medical device further comprises one of a stent, a graft anda stent-graft.
 10. The biocompatible implantable material according toclaim 7, wherein the structural member has at least on surface thereofhaving controlled heterogeneities thereupon.
 11. The biocompatibleimplantable material according to claim 8, wherein the monolithic bulkmaterial is selected from the group consisting of titanium, vanadium,aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon,magnesium, niobium, scandium, platinum, cobalt, palladium, manganese,molybdenum and alloys thereof, zirconium-titanium-tantalum alloys,nitinol, and stainless steel.
 12. The biocompatible implantable materialaccording to claim 7, further comprising an adsorptive layer betweenadjacent layers of the plural layers.